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An effective therapeutic approach for oxaliplatin-induced peripheral neuropathy using a combination therapy with goshajinkigan and bushi.
Cancer Biol Ther. 2016 11; 17(11):1206-1212.CB

Abstract

Oxaliplatin-induced peripheral neuropathy (OIPN) occurs at extraordinarily high frequency, but no effective treatment for this disorder has been established. Goshajinkigan (GJG), a traditional Japanese medicine known as Kampo, is known to reduce OIPN in both basic and clinical studies. However, its molecular mechanisms remain largely unknown. Here, we elucidate the mechanisms underlying the therapeutic effects of GJG against OIPN and the therapeutic benefits of combining GJG with bushi, a herbal medicine derived from the processed Aconiti tuber. Oxaliplatin (4 mg/kg) was injected into mice twice a week for up to 4 and 3 weeks, respectively. OIPN was assessed using pain behavioral tests, such as those testing cold hypersensitivity, thermal hyperalgesia, and mechanical allodynia, as well as a reduction of the current perception threshold (CPT). GJG (0.3 or 1 g/kg) and bushi (0.1 or 0.3 g/kg) were orally administered 5 times a week for 4 weeks. Behavioral analysis was performed 24 h after the final dose. Oxaliplatin induced cold hypersensitivity and mechanical allodynia but not thermal hyperalgesia and reduced CPT of Aδ- and Aβ-fibers but not C-fibers. All these effects were counteracted by GJG. Bushi, an ingredient of GJG that shows analgesic effect, reduced oxaliplatin-induced cold hypersensitivity but had no effect on oxaliplatin-induced mechanical allodynia. However, bushi significantly accentuated the effects of GJG when co-administered with GJG. GJG reduces OIPN by counteracting the sensitization of Aδ- and Aβ-fibers and shows analgesic effects against cold hypersensitivity and mechanical allodynia. These effects are potentiated by bushi. The combination of GJG with bushi has high potential for preventing OIPN.

Authors+Show Affiliations

a Tsumura Research Laboratories , Kampo Scientific Strategies Division, Tsumura & Co., Yoshiwara, Ami-machi , Inashiki-gun, Ibaraki , Japan.b Department of Neuropharmacology , Interdisciplinary Graduate School of Medicine, University of Yamanashi , Shimokato, Chuo, Yamanashi , Japan.b Department of Neuropharmacology , Interdisciplinary Graduate School of Medicine, University of Yamanashi , Shimokato, Chuo, Yamanashi , Japan.a Tsumura Research Laboratories , Kampo Scientific Strategies Division, Tsumura & Co., Yoshiwara, Ami-machi , Inashiki-gun, Ibaraki , Japan.a Tsumura Research Laboratories , Kampo Scientific Strategies Division, Tsumura & Co., Yoshiwara, Ami-machi , Inashiki-gun, Ibaraki , Japan.b Department of Neuropharmacology , Interdisciplinary Graduate School of Medicine, University of Yamanashi , Shimokato, Chuo, Yamanashi , Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27416484

Citation

Mizuno, Keita, et al. "An Effective Therapeutic Approach for Oxaliplatin-induced Peripheral Neuropathy Using a Combination Therapy With Goshajinkigan and Bushi." Cancer Biology & Therapy, vol. 17, no. 11, 2016, pp. 1206-1212.
Mizuno K, Shibata K, Komatsu R, et al. An effective therapeutic approach for oxaliplatin-induced peripheral neuropathy using a combination therapy with goshajinkigan and bushi. Cancer Biol Ther. 2016;17(11):1206-1212.
Mizuno, K., Shibata, K., Komatsu, R., Omiya, Y., Kase, Y., & Koizumi, S. (2016). An effective therapeutic approach for oxaliplatin-induced peripheral neuropathy using a combination therapy with goshajinkigan and bushi. Cancer Biology & Therapy, 17(11), 1206-1212.
Mizuno K, et al. An Effective Therapeutic Approach for Oxaliplatin-induced Peripheral Neuropathy Using a Combination Therapy With Goshajinkigan and Bushi. Cancer Biol Ther. 2016;17(11):1206-1212. PubMed PMID: 27416484.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An effective therapeutic approach for oxaliplatin-induced peripheral neuropathy using a combination therapy with goshajinkigan and bushi. AU - Mizuno,Keita, AU - Shibata,Keisuke, AU - Komatsu,Ryohei, AU - Omiya,Yuji, AU - Kase,Yoshio, AU - Koizumi,Schuichi, PY - 2016/7/15/pubmed PY - 2017/9/26/medline PY - 2016/7/15/entrez KW - Analgesic effect KW - bushi KW - combination therapy KW - goshajinkigan KW - oxaliplatin KW - peripheral neuropathy KW - traditional Japanese medicine SP - 1206 EP - 1212 JF - Cancer biology & therapy JO - Cancer Biol Ther VL - 17 IS - 11 N2 - Oxaliplatin-induced peripheral neuropathy (OIPN) occurs at extraordinarily high frequency, but no effective treatment for this disorder has been established. Goshajinkigan (GJG), a traditional Japanese medicine known as Kampo, is known to reduce OIPN in both basic and clinical studies. However, its molecular mechanisms remain largely unknown. Here, we elucidate the mechanisms underlying the therapeutic effects of GJG against OIPN and the therapeutic benefits of combining GJG with bushi, a herbal medicine derived from the processed Aconiti tuber. Oxaliplatin (4 mg/kg) was injected into mice twice a week for up to 4 and 3 weeks, respectively. OIPN was assessed using pain behavioral tests, such as those testing cold hypersensitivity, thermal hyperalgesia, and mechanical allodynia, as well as a reduction of the current perception threshold (CPT). GJG (0.3 or 1 g/kg) and bushi (0.1 or 0.3 g/kg) were orally administered 5 times a week for 4 weeks. Behavioral analysis was performed 24 h after the final dose. Oxaliplatin induced cold hypersensitivity and mechanical allodynia but not thermal hyperalgesia and reduced CPT of Aδ- and Aβ-fibers but not C-fibers. All these effects were counteracted by GJG. Bushi, an ingredient of GJG that shows analgesic effect, reduced oxaliplatin-induced cold hypersensitivity but had no effect on oxaliplatin-induced mechanical allodynia. However, bushi significantly accentuated the effects of GJG when co-administered with GJG. GJG reduces OIPN by counteracting the sensitization of Aδ- and Aβ-fibers and shows analgesic effects against cold hypersensitivity and mechanical allodynia. These effects are potentiated by bushi. The combination of GJG with bushi has high potential for preventing OIPN. SN - 1555-8576 UR - https://www.unboundmedicine.com/medline/citation/27416484/An_effective_therapeutic_approach_for_oxaliplatin_induced_peripheral_neuropathy_using_a_combination_therapy_with_goshajinkigan_and_bushi_ L2 - https://www.tandfonline.com/doi/full/10.1080/15384047.2016.1210742 DB - PRIME DP - Unbound Medicine ER -